Active Surveillance und die moderne Diagnostik des Prostatatkarzinoms

Zusammenfassung

Hintergrund

Ein Teil der Prostatakarzinome wird in der primären Prostatabiopsie nicht detektiert, sodass bei weiterbestehendem Verdacht eine erneute Biopsie erfolgen muss. Neben der Problematik der Falsch-negativ-Rate in der systematischen Biopsie, besteht eine hohe Missklassifikationsrate, insbesondere das Tumorgrading betreffend. Dadurch kann es zu einer verspäteten Diagnose aggressiverer Tumoreigenschaften und im ungünstigsten Falle zu einem Versäumnis kurativer Ansätze kommen. Aufgrund dieser Problematik bestehen zahlreiche Ansätze, die Therapieentscheidung und Überwachung durch den Einsatz moderner Bildgebung und genetischer Biomarker zu optimieren

Ziel

Der Beitrag vermittelt eine Übersicht über die Active-Surveillance(AS)-Definitionen, die Problematik der Prostatakarzinomdetektion und genaue Grading-Abschätzung in der systematischen transrektalen Biopsie und den Einsatz der multiparametrischen MRT (mpMRT), der gezielten MRT- Fusionsbiopsie und genetischer Biomarker als potenzielle Lösungsansätze sowie deren Integration im klinischen Alltag.

Material und Methoden

Aktuelle Literatur wurde recherchiert und im Kontext mit eigenen Erfahrungen ausgewertet.

Ergebnisse

Die mpMRT sowie die gezielte MRT-Fusionsbiopsie sind dem aktuellen Standard der systematischen Biopsie in der Detektion des klinisch signifikanten Prostatakarzinoms überlegen. Besonders deutlich zeigt sich dies im Falle der Wiederholungsbiopsie des anterioren Prostatakarzinoms, einer persistierend suspekten PSA-Dynamik und Einschluss und Monitoring von AS-Patienten. Auch die Kombination mit weiteren neuartigen Prädiktoren sind weitere vielversprechende Ansätze.

Schlussfolgerung

Der potenzielle diagnostische Mehrwert kann ausschließlich durch eine interdisziplinäre Verknüpfung der zunehmend komplexeren diagnostischen Schritte erreicht werden. Effektive Lösungen im Rahmen der interdisziplinären Zusammenarbeit von Radiologen und Urologen auf Niveau der Fachgesellschaften sind notwendig, um Fragen bezüglich des Zeitaufwands und der Ressourcenverteilung mit den Leistungserstattern zu adressieren.

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Issue Information ‐ TOC

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Corrigendum

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In this Issue: Graphical Abstracts

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Issue Information ‐ Cover and Editorial Board

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Expanding unilateral cochlear implantation criteria for adults with bilateral acquired severe sensorineural hearing loss

Abstract

Objectives

To report on a retrospective cohort study on the effects of expanding inclusion criteria for application of cochlear implants (CIs) on the performance 1-year post-implantation.

Methods

Based on pre-implantation audiometric thresholds and aided speech recognition scores, the data of 164 CI recipients were divided into a group of patients that fulfilled conservative criteria (mean hearing loss at 0.5, 1 and 2 kHz > 85 dB HL and phoneme scores with hearing aids < 30%), and the remaining group of patients that felt outside this conservative criterion. Speech recognition scores (in quiet) and quality of life (using the NCIQ) of both groups, measured at 1-year post-implantation, were compared.

Results

The group that felt outside the conservative criterion showed a higher phoneme score at 1-year post-implantation compared to the conservative group, suggesting that relaxed criteria have a positive influence on the speech recognition results with CI. With respect to quality of life, both groups significantly improved 1-year post-implantation. The conservative group showed a higher benefit on the advanced perception domain of the NCIQ. Based on their worse pre-implantation hearing, this was expected.

Conclusions

The data suggest that relaxation of CI indication positively affects the speech recognition performance of patients with severe hearing loss. Both groups of patients showed a positive effect of CI on the quality of life. This benefit relates to communication skills and the subjective day-to-day functioning in society.

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The role of heterogeneous environment and docetaxel gradient in the emergence of polyploid, mesenchymal and resistant prostate cancer cells

Abstract

The ability of a population of PC3 prostate epithelial cancer cells to become resistant to docetaxel therapy and progress to a mesenchymal state remains a fundamental problem. The progression towards resistance is difficult to directly study in heterogeneous ecological environments such as tumors. In this work, we use a micro-fabricated "evolution accelerator" environment to create a complex heterogeneous yet controllable in-vitro environment with a spatially-varying drug concentration. With such a structure we observe the rapid emergence of a surprisingly large number of polyploid giant cancer cells (PGCCs) in regions of very high drug concentration, which does not occur in conventional cell culture of uniform concentration. This emergence of PGCCs in a high drug environment is due to migration of diploid epithelial cells from regions of low drug concentration, where they proliferate, to regions of high drug concentration, where they rapidly convert to PGCCs. Such a mechanism can only occur in spatially-varying rather than homogeneous environments. Further, PGCCs exhibit increased expression of the mesenchymal marker ZEB1 in the same high-drug regions where they are formed, suggesting the possible induction of an epithelial to mesenchymal transition (EMT) in these cells. This is consistent with prior work suggesting the PGCC cells are mediators of resistance in response to chemotherapeutic stress. Taken together, this work shows the key role of spatial heterogeneity and the migration of proliferative diploid cells to form PGCCs as a survival strategy for the cancer population, with implications for new therapies.

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Management of cutaneous T‐cell lymphomas: Established and emergent therapies

Abstract

Cutaneous T‐cell lymphoma is an uncommon group of non‐Hodgkin's lymphoma primarily affecting the skin. It is comprised of a variety of entities with different clinical behaviours and prognosis. Mycosis fungoides is the commonest subtype, and Sézary syndrome is a much rarer form of cutaneous T‐cell lymphoma. At this stage, control rather than cure is the goal of therapy, with particular emphasis placed on preserving quality of life. Our review of the efficacy, safety profile and accessibility of treatment modalities for mycosis fungoides/Sézary syndrome is a tailored guide for the clinician treating these rare conditions.

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Management of cutaneous T‐cell lymphomas: Established and emergent therapies

Abstract

Cutaneous T‐cell lymphoma is an uncommon group of non‐Hodgkin's lymphoma primarily affecting the skin. It is comprised of a variety of entities with different clinical behaviours and prognosis. Mycosis fungoides is the commonest subtype, and Sézary syndrome is a much rarer form of cutaneous T‐cell lymphoma. At this stage, control rather than cure is the goal of therapy, with particular emphasis placed on preserving quality of life. Our review of the efficacy, safety profile and accessibility of treatment modalities for mycosis fungoides/Sézary syndrome is a tailored guide for the clinician treating these rare conditions.

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Assessment of the efficacy and safety of platelet poor plasma gel as autologous dermal filler for facial rejuvenation

Summary

Background

The popularity of dermal fillers has grown rapidly in the last few years for facial rejuvenation. Plasma gel is an autologous gelatinous material that is prepared from the patient's own platelet poor plasma.

Objective

To evaluate the clinical efficacy and safety of plasma gel injection as a dermal filler for facial rejuvenation.

Patients and Methods

The current study was carried out on 52 females presented with facial aging divided into two groups: Group A included 34 females with facial wrinkles, and Group B included 18 females with tear trough deformity. After taking written informed consent, they received two sessions of plasma gel injections at 2‐week interval and followed up monthly for 3 months. They were assessed clinically before treatment sessions and at the end of follow‐up period.

Results

Both studied groups showed immediate significant clinical improvement after plasma gel injection that maintained till the end of follow‐up period. This finding was confirmed by significant reduction in the mean values of Wrinkle Severity Rating Scale (WSRS) in Group A and Tear Trough Rating Scale (TTRS) in group B, and significant improvement of skin homogeneity and texture in both groups. In general, the reported side effects were minimal and transient.

Conclusion

Autologous platelet poor plasma gel injection seems to be a cost‐effective, safe, well‐tolerated, and minimally invasive technique producing significant aesthetic correction of facial wrinkles and tear trough deformity.

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Assessment of the efficacy and safety of platelet poor plasma gel as autologous dermal filler for facial rejuvenation

Summary

Background

The popularity of dermal fillers has grown rapidly in the last few years for facial rejuvenation. Plasma gel is an autologous gelatinous material that is prepared from the patient's own platelet poor plasma.

Objective

To evaluate the clinical efficacy and safety of plasma gel injection as a dermal filler for facial rejuvenation.

Patients and Methods

The current study was carried out on 52 females presented with facial aging divided into two groups: Group A included 34 females with facial wrinkles, and Group B included 18 females with tear trough deformity. After taking written informed consent, they received two sessions of plasma gel injections at 2‐week interval and followed up monthly for 3 months. They were assessed clinically before treatment sessions and at the end of follow‐up period.

Results

Both studied groups showed immediate significant clinical improvement after plasma gel injection that maintained till the end of follow‐up period. This finding was confirmed by significant reduction in the mean values of Wrinkle Severity Rating Scale (WSRS) in Group A and Tear Trough Rating Scale (TTRS) in group B, and significant improvement of skin homogeneity and texture in both groups. In general, the reported side effects were minimal and transient.

Conclusion

Autologous platelet poor plasma gel injection seems to be a cost‐effective, safe, well‐tolerated, and minimally invasive technique producing significant aesthetic correction of facial wrinkles and tear trough deformity.

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The impact of fertilizers on the uptake of manganese in Cherry Belle radish plants: implications for human health

Abstract

Miracle-Gro Singles, Miracle-Gro Shake and Feed, and Vigoro fertilizers are associated with net loss/enhancement of Mn, up to an order of magnitude when referenced to controls in soil, radish vegetables, and radish leaves; Mn enhancements are a factor of 4 to 65 below the daily required intake for humans (2–5.5 mg/day). Manganese levels were measured by atomic absorption spectrometry (AAS). Control soil, radish vegetables, and radish leaves contained 65 μg/g to 146 μg/g (median = 108), 65 μg/g to 357 μg/g (median = 281), and 185 μg/g to 401 μg/g (median = 323) of Mn, correspondingly. Manganese uptake was ten times greater in radish leaves compared to radish vegetables and enhanced by a factor of 3 in soils. Edible radish leaves/vegetables contain 65 times less than human Mn daily requirements. This equates eating 140 lb/day of radish vegetables/leaves. The fertilizers have a minor impact on Mn accumulation in radish leaves/vegetables. The USDA Nutrient Database for radish (0.69 μg/g of Mn) contradicts this notion as one would need to consume ~ 7 to 18 lb/day of radish to satisfy their daily intake. This study complements investigations showing that fertilizers induce minimal uptake of heavy metals in food; simultaneously, the net loss of Mn amounts observed in some samples of radish leaves and vegetables is analogous to the dilution effect of minerals/nutrients in edibles. Although a deficiency/excess of Mn in one's diet may lead to adverse health effects, background inhalation exposure in general public, occupational, and emergency response settings has a greater influence on one's propensity toward developing adverse health effects related to Mn inhalation exposure.

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Comprehensive review of acute oesophageal necrosis

Acute oesophageal necrosis, also known as 'black oesophagus', is a rare condition characterised by the black discolouration of the oesophageal mucosa on endoscopy and involves the distal oesophagus in majority of cases but may also extend proximally. A number of conditions are found to be associated with it and it is thought to occur due to a combination of hypovolaemia and inadequate oesophageal protective mucosal barrier function. Gastric secretions may have a direct effect on the oesophageal mucosa. We present a case of a woman who presented with haematemesis and significant hypotension after a session of haemodialysis. Black oesophagus was confirmed on esophagogastroduodenoscopy. She was given two units of packed red blood cells and one unit of platelets, and started on a pantoprazole infusion. However, despite rigorous attempts at resuscitation the patient failed to recover.

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Pharyngocutaneous fistula caused by dried 'Kombu (edible seaweed) after total laryngectomy

The most common early complication after total laryngectomy is pharyngocutaneous fistula (PCF). However, there are no reports of PCF after total laryngectomy caused by 'Kombu' (edible seaweed) as a foreign body in the digestive tract. A 68-year-old Japanese man had undergone total laryngectomy 5 years previously. He presented with PCF, neck swelling and pain. Video endoscopy showed that a dark green foreign body obstructed the digestive tract. PCF was successfully treated via emergency surgery comprising abscess drainage, foreign body removal and fistula closure. The foreign body was kombu. Clinicians who perform total laryngectomy should know the potential dangers of consuming hygroscopic food items that can cause bolus obstruction of the upper digestive tract and pharyngeal abscess and perforation.

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Thrombosis of abdominal aorta precipitating fatal subarachnoid haemorrhage

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Temporal bone involvement of IgG4-related disease: a rare condition misleading to petrous apicitis causing lateral rectus palsy

IgG4-related disease (IgG4-RD) of temporal bone is rare and clinical manifestation mimics infection. A 19-year-old female presented with progressive left earache and intermittent left nasal obstruction. Then, she rapidly developed left lateral rectus palsy. The physical examination revealed mild redness of left tympanic membrane and a small nasal polyp from the left middle meatus. CT scan showed left petrous apicitis and enhancing sinonasal mucosa. Therefore, Gradenigo's syndrome was first considered. The empirical intravenous antibiotic was immediately prescribed and surgery was performed. The intraoperative pale soft tissue mass in middle ear and polyp in the left nasal cavity were sent for pathological examination and found positive immunohistochemical stains for IgG4 in plasma cells. Systemic corticosteroid, the first-line treatment, was started and her symptoms were finally recovery.

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Endoscopic control of gastric emptying after administration of intravenous erythromycin in an awake patient scheduled for urgent rigid bronchoscopy

Certain interventional pulmonology procedures such as the placement of a tracheal stent or resection of stenosing tracheal tumours require rigid bronchoscopy under general anaesthesia. Unlike an endotracheal tube with a cuff, the rigid bronchoscope only partially protects the airway from bronchoaspiration. For this reason, this procedure is performed on an elective basis in fasted patients. We describe the case of a 60-year-old man with acute respiratory distress requiring emergent rigid bronchoscopy following distal migration of a tracheal stent. One hour before the procedure, the patient had eaten a full meal. Gastric emptying was accelerated by perfusion of intravenous erythromycin and verified by endoscopy with a small diameter gastric endoscope under local anaesthesia. This 1 min procedure was very well tolerated by the patient and allowed to verify with certainty that the stomach was empty. The urgent rigid bronchoscopy for stent retrieval could then be performed safely without any risk of bronchoaspiration.

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Case of autoimmune polyglandular syndrome type 2: how we uncovered the diagnosis

A 24-year-old man with no significant medical history presented to the medical clinic with vomiting and giddiness for 2 days, loss of appetite for 1 month and progressive fatigability for the preceding 4 months. On examination, he was found to be hypotensive and was admitted to the hospital for work-up. Considering his abnormal labs and physical findings, he was worked up and was diagnosed with primary adrenal insufficiency. On further work-up for the aetiology of his Addison's disease, he was found to have concurrent autoimmune thyroiditis and vitiligo. A final diagnosis of autoimmune polyglandular syndrome type 2 was made. The patient was started on hormone replacement therapy and reported improvement of symptoms on 3-month follow-up visit.

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Uncommon presentation of medication-related osteonecrosis of the mandible in a patient with metastatic prostate cancer

An 82-year-old man with a background of prostate carcinoma and bony metastases presented with bilateral discharging neck fistulae. Two years prior to presentation, the patient had been treated with intravenous zoledronic acid for 1 year as part of chemotherapy. Intraoral examination revealed extensive bilateral medication-related osteonecrosis, with orocutaneous fistulae within the neck. Treatment comprised removal of loose necrotic bone sequestrae, debridement of the fistulae and long-term administration of antibiotics, vitamin E and pentoxifylline. Four weeks later, the orocutaneous fistulae had healed.

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Unusual complication of an Alaskan cruise: thinking outside the box

A 69-year-old man with a medical history of hypertension and diabetes presented with altered mental status once he returned from a 14-day Alaskan cruise. An extensive workup for stroke was negative. His physical examination was normal without any focal motor deficits, but he had developed memory loss and paresthesia. He admitted to eating a lot of fish when he was in Alaska. The whole-blood mercury level was found to be elevated. He was managed conservatively and his symptoms resolved completely in a few days. This led to a diagnosis of organic mercury toxicity.

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Arterioportal fistula after partial gastrectomy treated with coil embolisation

Arterioportal fistulas are a rare complication of abdominal interventions. They can remain asymptomatic for a long time and manifest with symptoms of portal hypertension. We present the case of a 65-year-old man admitted to the emergency room with increasing fatigue and melena. He had a history of partial gastrectomy with Billroth II reconstruction 40 years earlier for peptic ulcer perforation. On physical examination, he was pale and presented a machinery-type murmur in the epigastric area. Blood tests revealed iron deficiency anaemia of 5.6 g/dL. During hospitalisation, he required several blood transfusions and maintained melenas. An abdominal CT angiography showed a fusiform aneurysm of the left gastric artery draining to the venous portal-splenic confluent. He was successfully treated with transarterial coil embolisation of the left gastric artery aneurysm. The correct diagnosis of arterioportal fistulas can be very challenging, whereas the standard treatment with coil embolisation offers a low morbidity resolution of symptoms.

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Rare mimic of recurrent anaphylaxis

The distinction between true anaphylaxis and conditions that mimic it can be challenging. We present the unique case of a 23-year-old woman treated for recurrent episodes of anaphylaxis over the course of 11 years and the subsequent discovery of an unlikely condition. We also discuss our approach in managing cases where an anaphylactic mimic is suspected.

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Paramedian chest wall dermoid cyst

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Endophthalmitis with bilateral deafness from disseminated Streptococcus suis infection

Streptococcus suis is a Gram-positive cocci bacterium that are found mainly in pigs and can be transmitted to human through pigs or pork exposure. The disease is mainly found among occupations involving swine contact in western countries whereas in Asia the disease is usually contracted through raw pork consumption. In this case report, we present a case of a middle-aged Thai man who acquired the infection from raw pork consumption. He presented with endogenous endophthalmitis with infective spondylodiscitis, sepsis and meningitis and later developed blindness of the right eye and permanent bilateral hearing loss disseminated from S. suis infection. Our report suggests that S. suis infection be considered as a causative factor in patient presenting with established clinical symptoms and predisposing factors. Cultural habit of eating raw pork should be taken into account especially in Asian countries.

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A pigmented and eroded lesion on the buttock

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A pigmented and eroded lesion on the buttock

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Global rosacea treatment guidelines and expert consensus points: The differences

Summary

Background

Rosacea is a highly prevalent, chronic inflammatory disease. The treatment of rosacea remains a challenge to dermatologists. Therapies include skin care, medications, lasers, and various combinations of these modalities. The appropriate treatment depends on clinical types and patient's various clinical symptoms.

Purpose

The purpose of this study was to review and compare current therapies for rosacea of all severities from four different guidelines.

Methodology

We searched PubMed using the keywords "rosacea," "treatment" AND ["erythema rosacea" OR "papulopustular rosacea" OR "ocular rosacea" OR "phymatous rosacea"]. We selected randomized controlled trials, observational studies, controlled clinical trials, and clinical trials. We indentified further studies (including the guidelines) by hand‐searching relevant publications and included those that met the inclusion criteria.

Results

The total number of records identified was 421. We limited our search to the specific abovementioned study types. Twenty‐five of these studies met with our inclusion criteria. An additional five manuscripts were selected using the abovementioned method, and four guidelines were included in this review.

Conclusion

Diagnosing and choosing the appropriate treatment options of rosacea according to guidelines is the basis of scientific criteria. More large‐scale randomized controlled clinical trials on new treatment methods, new drugs, or new dosage forms provide a new guideline for future rosacea treatment. Although there are some differences in the treatment of rosacea, it is generally based on anti‐demodex, anti‐inflammatory, and anti‐angiogenesis.

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Global rosacea treatment guidelines and expert consensus points: The differences

Summary

Background

Rosacea is a highly prevalent, chronic inflammatory disease. The treatment of rosacea remains a challenge to dermatologists. Therapies include skin care, medications, lasers, and various combinations of these modalities. The appropriate treatment depends on clinical types and patient's various clinical symptoms.

Purpose

The purpose of this study was to review and compare current therapies for rosacea of all severities from four different guidelines.

Methodology

We searched PubMed using the keywords "rosacea," "treatment" AND ["erythema rosacea" OR "papulopustular rosacea" OR "ocular rosacea" OR "phymatous rosacea"]. We selected randomized controlled trials, observational studies, controlled clinical trials, and clinical trials. We indentified further studies (including the guidelines) by hand‐searching relevant publications and included those that met the inclusion criteria.

Results

The total number of records identified was 421. We limited our search to the specific abovementioned study types. Twenty‐five of these studies met with our inclusion criteria. An additional five manuscripts were selected using the abovementioned method, and four guidelines were included in this review.

Conclusion

Diagnosing and choosing the appropriate treatment options of rosacea according to guidelines is the basis of scientific criteria. More large‐scale randomized controlled clinical trials on new treatment methods, new drugs, or new dosage forms provide a new guideline for future rosacea treatment. Although there are some differences in the treatment of rosacea, it is generally based on anti‐demodex, anti‐inflammatory, and anti‐angiogenesis.

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Inverse association between statin use and head and neck cancer: A population‐based case‐control study in Han population

Abstract

Background

This case‐control study aimed to find the relationship between prior statin use and head and neck cancer occurrence using a large population‐based database.

Methods

This study used claims data from the Taiwan Longitudinal Health Insurance Database. We included 5515 patients with head and neck cancer as cases and 5515 propensity score‐matched patients without head and neck cancer as controls. Conditional logistic regressions were performed to investigate the relationship between head and neck cancer and prior statin exposure.

Results

Of the 11 030 total sampled patients, 16.95% had previously received prescriptions for statins. In addition, statin exposure was found in 15.99% of cases and 17.91% of controls. The logistic regression also revealed that the adjusted odds ratio of prior statin exposure for cases was 0.86 (95% confidence interval: 0.77‐0.95) compared to propensity score‐matched controls.

Conclusion

This study found an inverse association between statin usage and head and neck cancer occurrence.

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Positive pressure device treatment for Menière’s disease: an overview of the current evidence and a meta-analysis

Abstract

Objective

The objective was to critically assess the current evidence investigating the efficacy of using a positive pressure device in patients with definite or probable Menière's disease.

Methods

We performed a systematic literature search in MEDLINE, EMBASE and PsycINFO up to February 2018. We included both systematic reviews and primary literature [randomized controlled trials (RCTs)] investigating positive pressure treatment, in patients (≥ 18 years of age), with Menière's disease. We assessed the internal validity of systematic reviews using the AMSTAR tool and risk of bias of primary studies using the Cochrane Risk of bias tool. We performed a meta-analysis for each outcome based on the identified studies. The overall certainty of evidence for the outcomes was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE).

Results

The search for systematic reviews identified four relevant reviews. These all included the same four RCTs. An updated search identified one additional RCT. In total, five RCTs were included in the data synthesis. Our data synthesis showed no effect of positive pressure treatment on primary nor secondary outcomes. No serious adverse events were reported. The overall certainty of evidence ranged from very low to low, due to the serious risk of bias and imprecision.

Conclusion

The current available evidence does not support positive pressure device treatment in patients with Menière's disease. However, the limitations of the current literature hinder the possibility of any solid conclusion. There remains a need for randomized controlled trials of high quality to fully access the utility of this treatment.

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Predictors of Success of Phase II Pediatric Oncology Clinical Trials

AbstractBackground.There are limited data to predict which novel childhood cancer therapies are likely to be successful. To help rectify this, we sought to identify the factors that impact the success of phase II clinical trials for pediatric malignancies.Materials and Methods.We examined the impact of 24 preclinical and trial design variables for their influence on 132 phase II pediatric oncology clinical trials. Success was determined by an objective assessment of patient response, with data analyzed using Fisher's exact test, Pearson's chi‐square test, and logistic regression models.Results.Trials that evaluated patients with a single histological cancer type were more successful than those that assessed multiple different cancer types (68% vs. 47%, 27%, and 17% for 1, 2–3, 4–7, and 8+; p < .005). Trials on liquid or extracranial solid tumors were more successful than central nervous system or combined trials (70%, 60%, 38%, and 24%; p < .005), and trials of combination therapies were more successful than single agents (71% vs. 28%; p < .005). Trials that added therapies to standard treatment backbones were more successful than trials testing novel therapies alone or those that incorporated novel agents (p < .005), and trials initiated based on the results of adult studies were less likely to succeed (p < .05). For 61% of trials (80/132), we were unable to locate any relevant preclinical findings to support the trial. When preclinical studies were carried out (52/132), there was no evidence that the conduct of any preclinical experiments made the trial more likely to succeed (p < .005).Conclusion.Phase II pediatric oncology clinical trials that examine a single cancer type and use combination therapies have the highest possibility of clinical success. Trials building upon a standard treatment regimen were also more successful. The conduct of preclinical experiments did not improve clinical success, emphasizing the need for a better understanding of the translational relevance of current preclinical testing paradigms.Implications for Practice.To improve the clinical outcomes of phase II childhood cancer trials, this study identified factors impacting clinical success. These results have the potential to impact not only the design of future clinical trials but also the assessment of preclinical studies moving forward. This work found that trials on one histological cancer type and trials testing combination therapies had the highest possibility of success. Incorporation of novel therapies into standard treatment backbones led to higher success rates than testing novel therapies alone. This study found that most trials had no preclinical evidence to support initiation, and even when preclinical studies were available, they did not result in improved success.

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Cost of Disease Progression in Patients with Chronic Lymphocytic Leukemia, Acute Myeloid Leukemia, and Non‐Hodgkin's Lymphoma

AbstractIntroduction.To reduce health care costs and improve care, payers and physician groups are switching to quality‐based and episodic or bundled‐care models. Disease progression and associated costs may affect these models, particularly if such programs do not account for differences in disease severity and progression risk within the cohort. This study estimated the incremental cost of disease progression in patients diagnosed with chronic lymphoid leukemia (CLL), acute myeloid leukemia (AML), and non‐Hodgkin's lymphoma (NHL) and compared costs among patients with and without progression.Methods.This was a retrospective study using U.S. administrative claims data from commercial and Medicare Advantage health care enrollees with evidence of CLL, AML, and NHL and systemic antineoplastic agent use from July 1, 2006 to August 31, 2014. Outcome measures included disease progression, 12‐month health care costs, and 3‐year cumulative predictive health care costs.Results.Of 1,056 patients with CLL, 514 patients with AML, and 7,601 patients with NHL, 31.1% of patients with CLL, 63.8% of those with AML, and 36.9% of those with NHL had evidence of disease progression. Among patients with CLL and NHL, adjusted and unadjusted health care costs were significantly higher among progressors versus nonprogressors. Per‐patient‐per‐month costs, accounting for variable follow‐up time, were almost twice as high among progressors versus nonprogressors in patients with CLL, AML, and NHL. In each of the three cancer types, the longer disease progression was delayed, the lower the health care costs.Conclusion.Progression of CLL, AML, and NHL was associated with higher health care costs over a 12‐month period. Delaying cancer progression resulted in a substantial cost reduction in patients with all three cancer types.Implications for Practice.Data on the rates and incremental health care costs of disease progression in patients with hematologic malignancies are lacking. This study estimated the incremental costs of disease progression in patients diagnosed with chronic lymphocytic leukemia, acute myeloid leukemia, and non‐Hodgkin's lymphoma and compared health care costs in patients with and without evidence of disease progression in a real‐world population. The data obtained in this study will assist future studies in quantifying the cost impact of decreased progression rates and will inform payers and physician groups about setting rates for episode and bundled payment programs.

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Coblator-Assisted Endoscopic Transnasal Resection of a Large Nasopharyngeal Pleomorphic Adenoma

Background. Pleomorphic adenomas occurring in the adult nasopharynx are rare, with our literature search identifying only 11 previous English-language reports. We document the unusual case of a large nasopharyngeal pleomorphic adenoma that was resected using radiofrequency coblation via an endoscopic transnasal approach. Methods. A 39-year-old male presented with worsening nasal congestion, intermittent otalgia, and a progressive change in voice. Flexible nasendoscopy showed a large homogeneous mass occupying the postnasal space, and computed tomography confirmed a 28 × 31 × 22 mm nasopharyngeal tumour. The biopsy-proven benign tumour was locally dissected using a coblator-assisted transnasal approach. Results. Histology confirmed complete excision of a myoepithelial-rich pleomorphic adenoma. The patient was symptom-free postoperatively, and no signs of recurrence were seen at one-year follow-up. Conclusions. This is a useful addition to the existing literature on surgical procedures used to treat benign pathology in the nasopharynx. The minimally invasive technique was well tolerated and had favourable patient outcomes.

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Carcinoma Erysipeloides From Metastatic Cutaneous Squamous Cell Carcinoma Initially Mistaken for Intralymphatic Histiocytosis

Abstract: Intralymphatic histiocytosis is a rare dermatologic disorder, commonly associated with inflammatory disorders and rarely malignancy. Carcinoma erysipeloides (CE) is a rare pseudoinflammatory cutaneous eruption that resembles soft -tissue infections as result of intralymphatic metastasis and subsequent lymphatic obstruction. Breast carcinoma represents most of the CE cases, but rarely other malignancies are involved. This report discusses a patient with a history of cutaneous squamous cell carcinoma (SCC) of the temple, who was initially diagnosed with intralymphatic histiocytosis located on his upper extremity, resistant to treatment. Further dermatologic and pathologic review later revealed metastatic SCC restricted to the dermal lymphatics, creating a CE reaction, initially obscured by intralymphatic histiocytes. This case highlights the difficulty in diagnosing metastatic carcinoma when the malignant cells are accompanied by a dense histiocytic infiltrate. The case demonstrates a rare presentation of CE due to metastatic cutaneous SCC and highlights the need for persistent investigation when confronted with nonconforming pathology. Correspondence: Michael S. Heath, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239 (e-mail: heatmi@ohsu.edu). The authors declare no conflicts of interest. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2SpxDdT

Polypoid Compound Melanocytic Proliferations: A Clinicopathological Study

Abstract: Nevi can show a polypoid appearance both clinically and histologically. Anecdotally, polypoid compound melanocytic nevus may exhibit a spectrum of junctional architectural and cytologic atypia, at times creating a diagnostic challenge by mimicking the radial growth phase of melanoma. To investigate this issue, we prospectively reviewed 40 polypoid compound melanocytic proliferations without overt malignant features. The lesions frequently occurred in young female patients and were predominantly from the trunk and intertriginous areas. Commonly observed atypical features included asymmetry (30%), shouldering (47.5%), poor circumscription (37.5%), and deep extension of melanocytes along the adnexal structures (67.5%). Severe cytologic junctional atypia (22.5%), dermal mitoses (10%), and pagetoid spread of melanocytes (5%) were less commonly seen. All lesions showed a reassuring dermal component with negligible cytologic atypia and maturation with depth. Overall, 7 lesions could not be readily classified as benign nevus; 5 of these in which a benign diagnosis was strongly favored were classified as atypical polypoid compound melanocytic nevi, whereas 2 lesions with diffuse severe junctional cytologic atypia and dermal mitoses were classified as ambiguous melanocytic proliferations. Atypical/ambiguous lesions were significantly larger and predominantly located in the axilla and groin. On molecular studies, none of the lesions tested showed the molecular profile of melanoma. We confirmed that polypoid compound melanocytic nevus can exhibit a variable degree of junctional atypia, likely related to frequent episodes of trauma and regeneration resulting in melanocytic proliferation. Pathologists should be aware of this phenomenon to avoid overdiagnosis. Correspondence: Nima Mesbah Ardakani, MD, FRCPA, Department of Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Perth, Western Australia 6009, Australia (e-mail: Nima.MesbahArdakani@health.wa.gov.au). The authors declare no conflicts of interest. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2XpYABN

Renal Cell Carcinoma Antigen Expression in Primary Cutaneous Endocrine Mucinous Carcinomas: A Case Series of 14 Patients and Review of the Literature

Abstract: Endocrine mucin-producing sweat gland carcinoma (EMPSGC) and primary cutaneous mucinous carcinoma (PCMC) are both uncommon low-grade cutaneous adnexal tumors with predilection for the eyelids of elderly women. Their clinical appearance is nonspecific, typically presenting as a slowly growing poorly circumscribed papule, nodule, plaque, or swelling. Histological features of EMPSGC include a lobulated dermal neoplasm with bland cytology and an invasive mucinous component in up to half of the cases. PCMC exhibits tumor nests suspended in abundant pools of mucin with focal strands or nests of tumor cells infiltrating the dermis. Because of their rarity and banal cytological features, both entities pose a risk for misdiagnosis with other benign/malignant cutaneous adnexal neoplasms. Histomorphological features can suggest a diagnosis of EMPSGC or PCMC, but immunohistochemistry is necessary for confirmation. A review of the literature showed variable results of antigens present in EMPSGC, and many of the positive markers only show sparse or focal immunoreactivity of tumor cells. As a result, diffusely positive markers play a crucial role in identification of these tumors, particularly with initial superficial biopsies. We present 9 cases of EMPSGC and 5 cases of PCMC with strong and diffuse immunoreactivity to renal cell carcinoma antigen. This novel finding can be useful in the diagnosis of EMPSGC and PCMC in combination with other known positive markers to differentiate them from other cutaneous neoplasms. In addition, it provides further evidence that EMPSGC could be a precursor lesion to PCMC with both existing on a spectrum. Correspondence: Carlos A. Cerruto, MD, FCAP, 1923 Lake Markham Preserve Trail, Sanford, FL 32771 (e-mail: cerrutomd@msn.com). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2SpxzuF

Primary Cutaneous Acral CD8+ T-Cell Lymphoma—A Single Center Review of 3 Cases and Recent Literature Review

Abstract: The recently published 2016 revision of the WHO classification of lymphoid neoplasms includes primary cutaneous acral CD8-positive T-cell lymphoma (PCATCL) as a provisional entity. This is a rare indolent lymphoma characterized by papules or nodules on the ear and a dermal infiltrate of CD8-positive T-lymphocytes with cytotoxic marker expression. A retrospective review of a single institutional experience with PCATCL identified 3 patients (mean age 54; range 49–62) with papules or nodules on the ear. Lesional biopsies demonstrated a dense diffuse dermal infiltrate of atypical lymphocytes with a Grenz zone in 2 cases and focal epidermotropism in 1 case. The atypical lymphocytes were predominantly CD3 and CD8 positive with expression of cytotoxic marker TIA1. Staging evaluation failed to reveal systemic disease. Two patients underwent local excision, and the third received local radiation therapy all with complete response and no disease recurrence at last follow-up 3 months (range 2–5 months). Our cases add to the existing limited literature on the clinical and histopathological features of PCATCL. We also performed an updated systematic literature view of the entity. Correspondence: Nneka I. Comfere, MD, 200 First Street SW, Rochester, MN 55905 (e-mail: comfere.nneka@mayo.edu). The authors declare no conflicts of interest. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2Xq9RlO

Coexistence of a Basal Cell Carcinoma and Leiomyosarcoma: An Unusual Collision Tumor

No abstract available

https://ift.tt/2St3xpF

Fibrosarcomatous Change in a Dermatofibrosarcoma Protuberans: Significance and Implications in the Differential Diagnosis of the Coexpression of S100 Protein and CD34 in Both Components

No abstract available

https://ift.tt/2XmKpO5

Global PD-L1 Signals and Tumor-Infiltrating Lymphocytes: Markers of Immunogenicity in Different Subsets of Merkel Cell Carcinoma and Potential Therapeutic Implications

Abstract: We previously studied the genetic and immunohistochemical profiles of subsets of Merkel cell carcinoma (MCC) stratified by morphology and Merkel cell polyomavirus (MCPyV) status. Recent advances in the immunotherapy of this disease prompted us to examine markers of immunogenicity [PD-L1 expression and tumor-infiltrating lymphocytes (TILS) in these subsets]. The observed clinical responses to checkpoint inhibition of the PD-1/PD-L1 pathway have not correlated with PD-L1 expression by MCC cells, and recent evidence suggests that functions of this pathway within the immune tumor microenvironment may be relevant. We conducted a semiquantitative (high, moderate, and minimal) immunohistochemical evaluation of the global PD-L1 signal in 52 cases of MCC, segregated in 3 subsets [pure MCPyV-positive (n = 28), pure MCPyV-negative (n = 9), and combined MCPyV-negative (n = 15)]. TILS were categorized as brisk, nonbrisk, or absent. Intersubset comparisons revealed that high global PD-L1 signals were exclusively associated with pure MCPyV-positive MCCs contrasted with virus-negative cases (P = 0.0003). Moderate signals were seen across all 3 groups. Brisk TILS were significantly associated with MCPyV-positive MCCs compared with MCPyV-negative cases (P = 0.029). Neither parameter (PD-L1 or TILS) was significantly different between the MCPyV-negative groups. Of potential clinical relevance, MCPyV seems to convey greater immunogenicity to MCCs than the high mutational burden/greater neoantigen load of MCPyV-negative cases. Interesting too is the fact that subset-related profiles of these markers mirrored those noted at genetic and immunohistochemical levels, separating pure MCPyV-positive MCCs from the virus-negative subsets. Correspondence: Noreen M. Walsh, MD, FRCPC, FRCPath (UK), Division of Anatomical Pathology, Rm 721, Nova Scotia Health Authority (QEII Site), Mackenzie Building, 5788 University Avenue, Halifax, NS B3H 1V8, Canada (e-mail: Noreen.walsh@nshealth.ca). Supported by research grants from the Nova Scotia Health Authority Research Fund and the DPLM Fund for Molecular Pathology housed at the QE II Foundation. The authors declare no conflicts of interest. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2SttLbA

A Rare Soft-Tissue Tumor in a 15-Year-Old Boy With Tuberous Sclerosis Complex: Challenge

No abstract available

https://ift.tt/2XnJEUJ

Observational Study Examining the Diagnostic Practice of Ki67 Staining for Melanocytic Lesions

Background: Dermatopathologists routinely use Ki67 immunostaining to assess atypical melanocytic lesions with a dermal component to determine whether an ambiguous tumor is melanoma. However, there is no universal standard of use for Ki67 in melanocytic neoplasms. We sought to observe the real-world use of Ki67 in the diagnosis of melanocytic lesions and establish a best practice recommendation. Methods: We searched dermatopathology reports from 2 academic practices for melanocytic lesions in which Ki67 staining was used for diagnosis. The proliferation rate was compared between cases diagnosed as benign (not requiring re-excision), moderate to severely dysplastic or atypical Spitz nevi (requiring re-excision), and malignant melanoma. The use of other melanocytic markers and consensus review was also recorded and compared between institutions. Results: Pathology reports for 106 cases were reviewed. A high Ki67 proliferation rate (n = 18) favored a diagnosis of melanoma or nevi requiring re-excision (15/18, 83.3%) versus a benign nevus (3/18, 16.67%). A high Ki67 rate was 71.4%–90.9% sensitive and 40%–56% specific for the diagnosis of nevus requiring re-excision or melanoma. Institutional practices differed in regard to reporting of Ki67 staining, the use of multiple markers in the workup of atypical melanocytic lesions (HMB45, Melan-A, Ki67 being most common), and consensus review. Conclusions: A negative or low Ki67 proliferation rate correlates well with rendering of a benign diagnosis. However, a low proliferation rate does not preclude the diagnosis of melanoma. Ki67 staining is most commonly used as an ancillary test to support a diagnosis after other factors have been considered, such as histopathologic morphology and results of additional concurrently used stains. Correspondence: Nikki S. Vyas, MD, Icahn School of Medicine at Mount Sinai, Department of Pathology, 1468 Madison Avenue, Box 1194, New York, NY 10029 (e-mail: nikki.vyas@mountsinai.org). The authors declare no conflicts of interest. Dr Vyas received a 2017 Mentorship Award from the American Society of Dermatopathology (ASDP) for work on this project. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2Sx3vNS

Cutaneous Crospovidone: A Newly Described Foreign Body Due to Illicit Drug Abuse

Abstract: Crospovidone, a polymer of poly N-vinyl-2-pyrrolidone, is an inert insoluble disintegrant found in pharmaceutical tablets. This material has been encountered in the lungs of intravenous drug users and embolized with other components such as talc and microcrystalline cellulose. More recently, crospovidone has also been described in the gastrointestinal tract. We present 2 cases of cutaneous crospovidone deposition resulting from subcutaneous injection of crushed tablets, commonly known as "skin popping." Clinical presentation includes painful, inflamed papules, nodules, or ulcers with overlying eschar. Crospovidone has a distinct and reproducible histochemical staining profile. Histologic recognition of this material is important because it can guide clinicians in their diagnosis and management decisions. Correspondence: Konstantinos D. Linos, MD, Division of Dermatopathology, Department of Pathology and Laboratory Medicine, One Medical Center Drive, Lebanon, NH 03766 (e-mail: Konstantinos.D.Linos@hitchcock.org). The authors declare no conflicts of interest. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2XpHXGt

Extramammary Paget Disease—A Challenging Case

No abstract available

https://ift.tt/2Sq5BPj

Vertical variation of bulk and metabolically active prokaryotic community in sediment of a hypereutrophic freshwater lake

Abstract

This study was conducted to acquire novel insight into differences between bulk (16S rDNA) and metabolically active (16S rRNA) prokaryotic communities in the sediment of a hypereutrophic lake (Japan). In the bulk communities, the class Deltaproteobacteria and the order Methanomicrobiales were dominant among bacteria and methanogens. In the metabolically active communities, the class Alphaproteobacteria and the order Methanomicrobiales and the family Methanosaetaceae were frequently found among bacteria and methanogens. Unlike the bulk communities of prokaryotes, the composition of the metabolically active communities varied remarkably vertically, and their diversities greatly decreased in the lower 20 cm of sediment. The metabolically active prokaryotic community in the sediment core was divided into three sections based on their similarity: 0–6 cm (section 1), 9–18 cm (section 2), and 21–42 cm (section 3). This sectional distribution was consistent with the vertical pattern of the sedimentary stable carbon and nitrogen isotope ratios and oxidation–reduction potential in the porewater. These results suggest that vertical disturbance of the sediment may influence the communities and functions of metabolically active prokaryotes in freshwater lake sediments. Overall, our results indicate that rRNA analysis may be more effective than rDNA analysis for evaluation of relationships between actual microbial processes and material cycling in lake sediments.

https://ift.tt/2tIQHJX

Familial oligodontia and regional odontodysplasia associated with a PAX9 initiation codon mutation

Abstract

Objective

Tooth agenesis is one of the most common craniofacial developmental anomalies. In hypodontia, one to five teeth are missing, whereas oligodontia refers to the absence of at least six teeth, excluding the third molars. Mutations in several genes including MSX1, PAX9, AXIN2, and WNT10A have been shown to cause non-syndromic tooth agenesis. Regional odontodysplasia (RO), also known as "ghost teeth," is a rare developmental anomaly of tooth formation affecting both dentitions. Some possible causes of RO have been suggested, yet the etiology remains unknown. Because the phenotypes of both oligodontia and RO co-occur in one Finnish family, the aim here was to investigate the genetic etiology of the two conditions.

Materials and methods

A mutation screening of the genes MSX1, PAX9, AXIN2, and WNT10A was performed for the family members of a RO patient and family history of oligodontia.

Results

An initiation codon mutation of the PAX9 gene was found in the proband and segregating with oligodontia in the family.

Conclusions

The etiology of regional odontodysplasia (RO) may be genetic and the same genes can be involved both in RO and tooth agenesis.

Clinical relevance

Our results give new insights into the etiology of regional odontodysplasia, yet further results are needed.

https://ift.tt/2Ntp6pv

Evaluation of underground hydraulic fracturing using transient electromagnetic method

Abstract

The effective area of hydraulic fracturing is the core index to evaluate its effects. Through conducting transient electromagnetic tests, this paper deals with the influential range of the underground hydraulic fracturing as well as water-cut detection and gas extraction in the fracturing area. The resistivity response law of the coal seam in hydraulic fracturing process is explored, and the water-bearing area is determined. The obtained results from the tests show that the water-cut areas of the coal seam, measured by anti-interference transient electromagnetic instrument after fracturing, are commonly placed in the low-resistance area of the transient test. Further, the variations of amplitude of the low-resistance area in various directions of the test line are different. According to the variation law of the apparent resistivity of the coal seam before and after fracturing, the effective influential area of the hydraulic fracturing is defined, and the influence range is evaluated to be 35 m. The water cut and the gas extraction tests of the coal seam before and after fracturing are performed. The results reveal that the growth of water content in the coal seam is inversely proportional to the distance from the hydraulic fracturing borehole. The effective fracturing zone with the increment of the water content reaching 0.2% is the effective fracturing zone, and the effective fracturing zone of #9 and #10 is 38 m. After hydraulic fracturing, the gas extraction concentration would be in the range of 25.4–75.4%, with the average of 70.22%, which is 21.22% higher than that of the original coal body. The net amount of the gas extraction after fracturing is about eight times of that before fracturing. The effective fracturing range, which is determined by transient electromagnetic, is verified successfully. Exploring the effective fracturing regions of the hydraulic fracturing process would be very helpful in improving the evaluation system of the hydraulic fracturing effect.

https://ift.tt/2NtAfq8

First-line therapy-stratified survival in BRAF-mutant melanoma: a retrospective multicenter analysis

Abstract

Background

Inhibition of the mitogen-activated protein kinase (MAPK) pathway as well as programmed death 1 receptor (PD-1) blockade was shown to prolong overall survival (OS) in patients with advanced B-Raf proto-oncogene (BRAF)-mutant melanoma. However, due to the lack of head-to-head trials, it remains unclear if one of these therapeutic approaches should be preferred in first-line therapy. Here, we present a retrospective analysis comparing anti-PD-1 monotherapy with BRAF/MAPK/ERK kinase (MEK) combined inhibition used as first-line agents in a real-world clinical setting.

Patients and methods

Clinical data, routine blood counts and lactate dehydrogenase (LDH) levels of 301 patients with unresectable or metastatic melanoma harboring an activating mutation in BRAF (V600E/K) were included. Of these, 106 received anti-PD-1 antibodies, while 195 patients were treated with a selective BRAF inhibitor combined with an MEK inhibitor as palliative first-line therapy. Patients were sub-grouped according to previously described predictive and prognostic markers.

Results

OS was significantly longer in patients receiving anti-PD-1 monotherapy compared to patients receiving combined MAPK inhibitors. Subsequent therapies were comparable among these groups. The difference in OS was less pronounced in patients with high LDH levels and visceral metastatic spread.

Conclusion

First-line treatment with a PD-1 blocking antibody might be associated with longer OS than first-line inhibition of the MAPK pathway in patients with advanced melanoma harboring mutant BRAF. These hypothesis-generating data need to be confirmed or rejected in prospective, randomized trials.

https://ift.tt/2Nw4Bs3

Expression of a soluble IL-10 receptor enhances the therapeutic effects of a papillomavirus-associated antitumor vaccine in a murine model

Abstract

The presence of IL-10, produced either by tumor cells or immunosuppressive cells, is frequently associated with a poor prognosis for cancer progression. It may also negatively impact anticancer treatments, such as immunotherapies, that otherwise would promote the activation of cytotoxic T cells capable of detecting and destroying malignant cells. In the present study, we evaluated a new adjuvant approach for anticancer immunotherapy using a plasmid vector encoding a soluble form of the IL-10 receptor (pIL-10R). pIL-10R was coadministered to mice with a DNA vaccine encoding the type 16 human papillomavirus (HPV-16) E7 oncoprotein genetically fused with glycoprotein D of herpes simplex virus (HSV) (pgDE7h). Immunization regimens based on the coadministration of pIL-10R and pgDE7h enhanced the antitumor immunity elicited in mice injected with TC-1 cells, which express HPV-16 oncoproteins. The administration of the DNA vaccines by in vivo electroporation further enhanced the anticancer effects of the vaccines, leading to the activation of tumor-infiltrating polyfunctional E7-specific cytotoxic CD8⁺ T cells and control of the expansion of immunosuppressive cells. In addition, the combination of immunotherapy and pIL-10R allowed the control of tumors in more advanced growth stages that otherwise would not be treatable by the pgDE7h vaccine. In conclusion, the proposed treatment involving the expression of IL-10R enhanced the antitumor protective immunity induced by pgDE7h administration and may contribute to the development of more efficient clinical interventions against HPV-induced tumors.

https://ift.tt/2GNJJMl

Endokrine Funktionsstörungen nach Bestrahlung von Hirntumoren bei Kindern und jungen Erwachsenen

https://ift.tt/2ICgFJK

Effects of septorhinoplasty on smell perception

Abstract

Purpose

To assess whether significant changes in smell perception occur after septorhinoplasty, and evaluate whether septum deviation, allergic rhinitis, and surgical technique affect postoperative smell perception.

Methods

Thirty-four patients (> 18 years old) awaiting septorhinoplasty were included, while those with previous severe hyposmia or anosmia were excluded. The participants self-assessed their smell perception using a 100-mm visual analogue scale (VAS), where 0 mm indicated the inability to smell and 100 mm indicated normal smell perception. The University of Pennsylvania Smell Identification Test (UPSIT) was applied before the procedure, and 4 and 12 weeks after surgery.

Results

The UPSIT score showed no significant changes at 4 (p = 0.59; 95% CI − 0.35 to + 2) or 12 weeks (p = 0.16; 95% CI − 1.13 to + 0.66). A comparison of the VAS scores before and 4 weeks after surgery (p = 0.62; 95% CI − 0.63 to + 0.39) yielded similar results. However, the average VAS scores improved 12 weeks after surgery (p = 0.007; 95% CI + 0.22 to + 1.30). Olfactory function, measured using the UPSIT, was not influenced by open or closed surgical techniques (p ≥ 0.10), the presence or absence of rhinitis (p ≥ 0.15), or obstructive septum deviation (p ≥ 0.38). Twelve weeks after surgery, self-evaluated smell perception was better in patients who underwent a closed procedure rather than an open procedure (p = 0.006; 95% CI: −1.39 to −0.37).

Conclusion

A validated test demonstrates that septorhinoplasty does not compromise smell perception 4 and 12 weeks after surgery. However, it might improve smell perception by the self-report observation.

https://ift.tt/2BS9OG2

Immunoregulatory Effects of Neuropeptides on Endothelial Cells: Relevance to Dermatological Disorders

Many skin diseases, including psoriasis and atopic dermatitis, have a neurogenic component. In this regard, bidirectional interactions between components of the nervous system and multiple target cells in the skin and elsewhere have been receiving increasing attention. Neuropeptides released by sensory nerves that innervate the skin can directly modulate functions of keratinocytes, Langerhans cells, dermal dendritic cells, mast cells, dermal microvascular endothelial cells and infiltrating immune cells. As a result, neuropeptides and neuropeptide receptors participate in a complex, interdependent network of mediators that modulate the skin immune system, skin inflammation, and wound healing. In this review, we will focus on recent studies demonstrating the roles of α-melanocyte-stimulating hormone, calcitonin gene-related peptide, substance P, somatostatin, vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, and nerve growth factor in modulating inflammation and immunity in the skin through their effects on dermal microvascular endothelial cells.
Dermatology

https://ift.tt/2EjKXv8

IMRT Combined With Toripalimab in Unresectable Locally Recurrent Nasopharyngeal Carcinoma.

Conditions:   Nasopharyngeal Carcinoma;   Nasopharyngeal Neoplasms;   Nasopharyngeal Diseases;   Head and Neck Neoplasm
Interventions:   Drug: Tolipalimab;   Radiation: Reirradiation
Sponsor:   Sun Yat-sen University
Not yet recruiting

https://ift.tt/2BSw7M2

Experimental Pain Reporting Accuracy and Clinical Post-operative Pain

Conditions:   Surgical Procedure, Unspecified;   Pain, Postoperative;   ENT Disease
Intervention:   Device: pain reporting accuracy
Sponsors:   Carmel Medical Center;   University of Haifa
Not yet recruiting

https://ift.tt/2UbDmpi

A Dose Escalation Study of PF‑06939999 in Participants With Advanced or Metastatic Solid Tumors.

Conditions:   Advanced Solid Tumors;   Metastatic Solid Tumors
Intervention:   Drug: PF-06939999
Sponsor:   Pfizer
Not yet recruiting

https://ift.tt/2BTUs45

Nivolumab and BMS986205 in Treating Patients With Stage II-IV Squamous Cell Cancer of the Head and Neck

Conditions:   Lip;   Oral Cavity Squamous Cell Carcinoma;   Pharynx;   Larynx;   Squamous Cell Carcinoma
Interventions:   Biological: Nivolumab;   Biological: IDO1 Inhibitor BMS-986205;   Procedure: Therapeutic Conventional Surgery;   Other: Questionnaire Administration
Sponsor:   Thomas Jefferson University
Not yet recruiting

https://ift.tt/2U8lcoj

Serial Epstein-Barr Virus DNA Surveillance in Nasopharyngeal Carcinoma Patients

Condition:   Nasopharyngeal Carcinoma
Intervention:   Diagnostic Test: Plasma EBV DNA
Sponsor:   Sun Yat-sen University
Not yet recruiting

https://ift.tt/2BTUokR

Study of TQB2450 in Patients With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck（R/M SCCHN）

Condition:   Squamous Cell Carcinoma of the Head and Neck
Interventions:   Drug: TQB2450+cisplatin or carboplatin + 5-Fluorouracil (5-FU);   Drug: placebo+cisplatin or carboplatin + 5-Fluorouracil (5-FU)
Sponsor:   Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Not yet recruiting

https://ift.tt/2U5q2ms

IMRT Combined With Toripalimab in Unresectable Locally Recurrent Nasopharyngeal Carcinoma.

Conditions:   Nasopharyngeal Carcinoma;   Nasopharyngeal Neoplasms;   Nasopharyngeal Diseases;   Head and Neck Neoplasm
Interventions:   Drug: Tolipalimab;   Radiation: Reirradiation
Sponsor:   Sun Yat-sen University
Not yet recruiting

https://ift.tt/2BSw7M2

Experimental Pain Reporting Accuracy and Clinical Post-operative Pain

Conditions:   Surgical Procedure, Unspecified;   Pain, Postoperative;   ENT Disease
Intervention:   Device: pain reporting accuracy
Sponsors:   Carmel Medical Center;   University of Haifa
Not yet recruiting

https://ift.tt/2UbDmpi

A Dose Escalation Study of PF‑06939999 in Participants With Advanced or Metastatic Solid Tumors.

Conditions:   Advanced Solid Tumors;   Metastatic Solid Tumors
Intervention:   Drug: PF-06939999
Sponsor:   Pfizer
Not yet recruiting

https://ift.tt/2BTUs45

Nivolumab and BMS986205 in Treating Patients With Stage II-IV Squamous Cell Cancer of the Head and Neck

Conditions:   Lip;   Oral Cavity Squamous Cell Carcinoma;   Pharynx;   Larynx;   Squamous Cell Carcinoma
Interventions:   Biological: Nivolumab;   Biological: IDO1 Inhibitor BMS-986205;   Procedure: Therapeutic Conventional Surgery;   Other: Questionnaire Administration
Sponsor:   Thomas Jefferson University
Not yet recruiting

https://ift.tt/2U8lcoj

Serial Epstein-Barr Virus DNA Surveillance in Nasopharyngeal Carcinoma Patients

Condition:   Nasopharyngeal Carcinoma
Intervention:   Diagnostic Test: Plasma EBV DNA
Sponsor:   Sun Yat-sen University
Not yet recruiting

https://ift.tt/2BTUokR

Study of TQB2450 in Patients With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck（R/M SCCHN）

Condition:   Squamous Cell Carcinoma of the Head and Neck
Interventions:   Drug: TQB2450+cisplatin or carboplatin + 5-Fluorouracil (5-FU);   Drug: placebo+cisplatin or carboplatin + 5-Fluorouracil (5-FU)
Sponsor:   Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Not yet recruiting

https://ift.tt/2U5q2ms

Treatment of intravitreal bevacizumab combined with focal laser photocoagulation in the case of macular telangiectasia type 2 with retinal arterial macroaneurysm

Abstract

Macular telangiectasia type 2 (Mac Tel 2) is a bilateral disease of unknown cause with characteristic changes of the retinal vasculature. To the best of our knowledge, we could not find any reported cases of Mac Tel 2 with retinal arterial macroaneurysm (RAM). Our aim is to report a case of Mac Tel 2 with RAM.

https://ift.tt/2VmWbpH

Comparative study of photodynamic activity of methylene blue in the presence of salicylic acid and curcumin phenolic compounds on human breast cancer

Abstract

Curcumin and salicylic acid are both phenolic compounds and they can both affect cancer treatment efficacy. In this study, the effects of methylene blue-curcumin (CU-MB) and methylene blue-salicylic acid (SA-MB) ion pair complexes on MDA-MB-231 human breast cancer cells are studied. According to the thermodynamic parameters, the stability of curcumin and salicylic acid complexes ion pair complexes was compared. The free energy of ion pair interactions was calculated based on binding constants. A comparison of the free energies of the complexes (CU-MB: ∆G^°_b1 = − 21.11 kJ/mol and ∆G^°_b2 = − 8.37 kJ/mol, SA-MB: ∆G^°_b1 = − 12.92 kJ/mol and ∆G^°_b2 = − 9.02 kJ/mol) indicates that the interaction of methylene blue in first binding interaction with curcumin is greater than that of methylene blue with salicylic acid. Electrostatic interactions are the main forces in the binding of both compounds to methylene blue. All forces are inter-molecular physical interactions. The results of cellular experiments show that ion pairing has enhanced the reduction of cell viability. By increasing molecular stability and prevention of dimerization of methylene blue, the cell killing potential of methylene blue increases and it subsequently causes enhancement of photodynamic efficacy.

https://ift.tt/2EyejHx

Correction to: Outpatient erbium:YAG (2940 nm) laser treatment for snoring: a prospective study on 40 patients

In the originally published article, the name of the first author was incorrectly labeled. Given name is Isabelle and family name is Fini Storchi.

https://ift.tt/2VfEuIG

Dental acid etchant as a sensitizing agent in photodynamic therapy to reduce S. mutans in dentinal carious lesions

Abstract

The study aims to assess the utility of dental acid etchant containing 37% phosphoric acid and methylene blue dye (DAE) as a sensitizing agent for photodynamic therapy (PDT) to reduce Streptococci mutans in dentinal caries. Forty-five permanent third molars were sectioned and the coronal dentin exposed. A cariogenic challenge was performed using brain-heart infusion (BHI) supplemented with 0.5% yeast extract, 1% glucose, 1% sucrose, and S. mutans ATCC 25175 standardized to 0.5 McFarland turbidity. Specimens were incubated in anaerobic jars at 37 °C for 15 days. During this period, BHI broth was renewed every 24 h. After 15 days, specimens were randomly divided into three groups (n = 15): DAE, application of dental acid etchant containing 37% phosphoric acid and methylene blue dye for 15 s; LLL, application of low-level laser (wavelength 660 nm, energy 4 J/cm², power 5 W) for 15 s; and PDT, application of DAE for 15 s followed by LLL irradiation (660 nm, 4 J/cm², 5 W). Carious tissue from each specimen was collected before and after the applications. Five decimal dilutions were performed and the resulting solution was seeded in mitis-salivarius-bacitracin agar. Plates were incubated in anaerobic jars at 37 °C for 48 h. Analysis of variance (ANOVA) with post hoc Tukey's test was used to compare total S. mutans counts. Significant reductions in S. mutans were observed after DAE application (40.70%, p < 0.0001), LLL (12.35%, p = 0.0036), and PDT (55.22%, p < 0.0001). Dental acid etchant containing 37% phosphoric acid and methylene blue dye can be used as a photosensitizing agent for PDT to reduce S. mutans burden in dentinal caries.

https://ift.tt/2EyxqBi

Influence of laser wavelength and beam profile on the coagulation depth in a soft tissue phantom model

Abstract

In laser tissue soldering (LTS), a protein solution is thermally denatured and cross-linked to obtain a strong bond between tissues or tissue and a wound dressing. However, if the extension of the heat-affected zone is too large, wound healing is impaired by thermal tissue injuries. Therefore, heat input and coagulation depth have to be limited. We investigate the influence of wavelength and beam profile on coagulation depth using a soft tissue phantom in case of weakly (980 nm) and strong (1540 nm) absorbed laser radiation. The soft tissue phantom is doped with polystyrene (PS) beads to obtain similar scattering properties as natural tissue. The propagation of the laser radiation in the phantom is simulated by Monte–Carlo method and the optical penetration (OPD) depth calculated from isophotes. The simulation results are compared with the experimental determination of the coagulation volume. The results reveal that scattering effect of tissues on laser radiation increases the losses of a Gaussian beam profile laterally leading to a half-sphere coagulation volume. The depth profile of the coagulation follows approximately the intensity distribution of the laser beams as long as scattering effects are weak. As scattering effects become significant, as for 980-nm radiation, the intensity distribution of the laser beam in the tissue deviates from the original one, leading to different profile of the coagulation depth.

https://ift.tt/2Vmg3t6

Examination of the cellular mechanisms of leukocyte elevation by 10.6 μm and 650 nm laser acupuncture-moxibustion

Abstract

To investigate the cell cycle and cellular mechanisms of leukocyte elevation by laser acupuncture in rats with cyclophosphamide (CTX)-induced leukopenia. Sixty-six rats were randomized into six groups: normal, model control group, sham treatment group, 10.6 μm laser treatment group, 650 nm laser treatment group, and 10.6 μm–650 nm compound laser treatment group. Eleven rats were used in the normal group and 55 were models that were injected with cyclophosphamide to induce leukopenia. For the three laser treatment groups, 10.6-μm and 650-nm lasers, and 10.6-μm–650-nm compound lasers were used to irradiate the DU14 (Dazhui) and bilateral ST36 (Zusanli) for 5 min each. The sham laser group received the same operation as the laser group but without irradiation. The normal group and model group were not treated. Differences in the number of nucleated cells in the femoral bone marrow, and cell cycle and cellular apoptosis of peripheral leukocytes in rats in various groups were compared. Compared with the model group and the sham laser group, the number of nucleated cells in the femoral bone marrow in the 10.6-μm laser, 650-nm laser, and 10.6-μm–650-nm compound laser group was significantly increased after treatment (P = 0.001, 0.002, 0.034, respectively) and did not show any significant difference with the normal group (P = 0.964, P = 0.838, P = 0.287, respectively). The number of cells in G2 phase in the 10.6 μm laser group was similar to that of the normal group (P = 0.973). The number of cells in G2 phase in the model, sham, 650-nm laser group, and 10.6-μm–650-nm compound laser group were significantly lower than in the normal group and 10.6-μm laser group (P = 0.016, P = 0.023, P = 0.044, P = 0.039, respectively). In the model group and the sham treatment group, the apoptosis rates of peripheral leukocytes were increased compared with the normal group (P = 0.001), while the proportion of cells in the G2 phase was significantly lower than in the normal group (P = 0.016), and the proportion of cells in S phase was higher than in the normal group (P = 0.014). The incidence of apoptosis in peripheral blood cells in the three laser treatment groups did not show any statistically significant difference when compared with the normal group (P > 0.05). Treatment with the 10.6-μm, 650-nm, and 10.6-μm–650-nm compound lasers increased the number of nucleated cells in the bone marrow, decreased the unfavorable effects of cyclophosphamide on the cell cycle, induced the cell cycle towards proliferation, decreased apoptosis, improved the intramedullary hematopoietic system, and increased peripheral leukocyte count.

https://ift.tt/2ExyZPX

Environmental etiology of gastric cancer in Iran: a systematic review focusing on drinking water, soil, food, radiation, and geographical conditions

Abstract

The aim of this systematic review study was to investigate the causal relationship between environmental factors and gastric cancer (GC) in Iran. In a narrow definition, the environment includes water, soil, air, and food. This definition was the main criterion for the inclusion of articles in this study. In addition, exposure to radiation and geographical conditions were considered as less investigated environmental factors in the literatures. International (PubMed, Web of Science, ScienceDirect, Scopus, and Cochran) and national (Scientific Information Database) databases were searched for articles on GC and environmental risk factors in Iran. Twenty-six articles were found to meet the inclusion criteria after title, abstract, and full text review. Risk factors identified for GC include consumption of red meat; high fat, fried, and salted meat; smoked, salted, and fried foods; some dairy products; roasted and fried seeds; strong and hot tea; and un-piped and unchlorinated drinking water, as well as exposure to radiation, loess sediment, soft and grassy soil, soil containing low concentration of molybdenum, and proximity to volcanos. Fresh fruits and vegetable, fresh fish, and honey consumption were recognized as protective agents. Given the risk factors identified, strategies to prevent GC would be educating people to choose a healthy diet and to cook and store food properly, providing access to safe drinking water, taking into account topographical and geographical conditions in choosing a right location to build residential areas, and regulating the use of radiation-emitting devices.

https://ift.tt/2SsWpJS

Aluminium foil dampened the adverse effect of 2100 MHz mobile phone–induced radiation on the blood parameters and myocardium in rats

Abstract

Mobile phones emit a radiofrequency radiation (RFR) that might have adverse health effects. We aimed to investigate the possible protective effects of aluminium foil (AF) as a physical shield against the RFR from mobile phones on the blood parameters and the myocardium in rats. The effects of whole body 2100 MHz with 0.84–1.86 W/kg of SAR, 4 h/day for 30 days Global System for Mobile Communications (GSM)-RFR exposure for 4 h/day for 30 days on blood parameters (i.e. haemoglobin, leucocytes, thrombocytes, erythrocyte sedimentation rate, white blood cell differential count, corticosterone, CKMB), and the histology of myocardium were investigated. Three-month-old male rats (n = 32) were studied and randomised equally in the following four groups: K1 (non-AF non-RFR control), K2 (AF non-RFR control), P1 (non-AF RFR-exposed), P2 (AF RFR-exposed). Data were analysed with level of significance of p < 0.05. In P1, lower leucocytes and neutrophils counts with high corticosterone levels were found compared with the control groups, whilst a significantly higher CKMB was observed compared with P2 (p = 0.034). Lower cardiomyocyte counts congruent to the area fraction of the non-fibrotic myocardium were observed in P1 compared with the other groups (p < 0.01). AF might decrease the inflammatory-oxidative stress on rodent's blood cells and myocardium induced by the exposures of radiofrequency radiation of the mobile phones.

https://ift.tt/2XmbfWB

Methylene blue dye removal on silver nanoparticles reduced by Kyllinga brevifolia

Abstract

Silver nanoparticles (AgNPs) were prepared by reacting Kyllinga brevifolia extract (KBE) with AgNO₃ aqueous solution at room temperature (22 ± 3 °C). The phytochemical constituents in KBE responsible for the reduction process were identified as carbohydrate, protein, and plant sterols (stigmasterol and campesterol). KBE was also found to function as a capping agent for stabilization of AgNPs. The AgNPs were stable at room temperature and had a quasi-spherical shape with an average particle size 22.3 nm. The use of KBE offers not only eco-friendly and non-pathogenic path for AgNPs formation, it also induced rapid formation of the AgNPs. Methylene blue (MB) removal was then done on the AgNPs in the presence of either KBE or NaBH₄. Ninety-three percent removal of MB was achieved with a rate of reaction 0.2663 min⁻¹ in the solution with KBE+AgNPs (pH 2). However, in NaBH₄+AgNPs system, 100% MB removal was achieved at pH 8–10. The reaction rate was 2.5715 min⁻¹ indicating a fast removal rate of MB dye. The process of reduction occurs via electron relay effect whereas in KBE+AgNPs system, sedimentation occurred along with the reduction process. Nevertheless, the use of KBE+AgNPs system is preferred as the reducing agent is more benign to the environment.

https://ift.tt/2SqXTEM

Clonal analysis of early-stage bilateral papillary thyroid cancer identifies field cancerization

Abstract

Introduction

Bilaterality is a newly identified indicator for aggressive tumor behavior and poor outcome in papillary thyroid cancer. However, the clonal origin of these bilateral tumors remains unclear.

Methods

Here we analyzed 28 pairs of early-stage papillary thyroid cancers (stage I–II without extra-thyroidal extension, lymph node metastasis or distant metastasis) that underwent surgery at First Affiliated Hospital of Zhejiang University School of Medicine (Hangzhou, China). Genomic DNA was extracted from paraffin-embedded tissues after microdissection and analyzed for BRAF mutation and X-chromosome inactivation.

Results

A total of 16 patients (16/28, 57.1%) harbored different BRAF status in bilateral tumors. Fourteen patients were available for X-chromosome inactivation assay and 10 of them achieved informative results. Bilateral tumors from four cases had distinct patterns of X-chromosome inactivation. Combining the results of X-chromosome inactivation and BRAF analysis, we demonstrated that at least 64.3% (18/28) cases harbored discordant X-chromosome inactivation or BRAF status, indicating their independent clonal origin in bilateral tumors.

Conclusions

The present study confirms "field cancerization" in early-stage bilateral thyroid cancers, suggesting that these subtype papillary thyroid cancers should be treated as independent and localized tumors.

https://ift.tt/2GM6lge

The impact of intravenous isotonic and hypotonic maintenance fluid on the risk of delirium in adult postoperative patients: retrospective before-after observational study

Abstract

Purpose

To assess the impact of intravenous isotonic and hypotonic maintenance fluid on the risk of delirium in adult postoperative patients, we conducted retrospective before-after study in a tertiary teaching hospital.

Methods

We examined all adult patients admitted ICU after an elective operation for head and neck cancer, or esophageal cancer from February 2014 to January 2017. From February 2014 to July 2015, patients were administered hypotonic fluid (sodium; 35 mmol/L) as the National Institute for Health and Care Excellence (NICE) have recommended. From August 2015 to January 2017, patients were administered isotonic fluid (sodium; 140 mmol/L). We defined the incidence of delirium as the primary outcome. The delirium was defined as the Intensive Care Delirium Screening Checklist during the ICU stay ≥ 4. A propensity score-matched model was used to adjust confounders.

Results

As postoperative intravenous maintenance fluid, hypotonic fluid was administered to 119 patients and isotonic fluid was administered to 92 patients. Among those total cohorts, the incidence of postoperative delirium in the hypotonic group was 21.8%, which was significantly higher than that (9.8%) in the isotonic group (p = 0.019). After propensity score matching, we selected 77 patients in each group. The incidence of delirium during the ICU stay in the hypotonic group was 26.0%, which was significantly higher than the incidence of 11.7% in the isotonic group (p = 0.023).

Conclusions

In this study, the use of postoperative hypotonic maintenance fluid was associated with a higher risk of postoperative delirium than that when isotonic maintenance fluid was used.

https://ift.tt/2GKZpjv

Experimental research on the therapeutic effect of MMR vaccine to juvenile-onset recurrent respiratory papillomatosis

Abstract

Objective

To evaluate the efficacy of MMR vaccine in the treatment of juvenile-onset recurrent respiratory papillomatosis as adjuvant therapy by experimental research.

Methods

Thirty-one children with RRP were enrolled and assigned randomly to intervention group or control group. Fifteen subjects in intervention group were treated with local application MMR vaccine on the lesion after surgery; sixteen subjects in the control group were treated with surgical excision alone. The quantity of virus of positive specimens was measured by fluorescence quantitative polymerase chain reaction.

Results

After treatment with MMR vaccine, viral load of intervention group was (9.56 ± 11.03) × 10⁸  copies/ml, that of control group was (22.01 ± 17.78) × 10⁸ copies/ml, and there was significant difference between the two groups (P = 0.040).

Conclusions

Local application MMR vaccine as adjuvant therapy can reduce HPV viral load significantly. It is suggested that the MMR vaccine may inhibit replication of HPV DNA, but the curative effect needs further confirmation.

https://ift.tt/2NsUT9S

Bilateral Syphilitic Optic Neuropathy with Secondary Autoimmune Optic Neuropathy and Poor Visual Outcome

We describe the case of a 65-year-old man who suffered progressive visual loss despite appropriate treatment of ocular syphilis. Our patient initially presented with a unilateral 6th nerve palsy and associated double vision, which self-resolved over 6 months. His ophthalmic examination was otherwise normal. 12 months after the initial complaint, he represented with dyschromatopsia, reduced visual acuity, tonic pupils, and optic nerve atrophy. He tested positive for syphilis and was admitted for treatment of neurosyphilis with high-dose benzylpenicillin. Despite treatment, at a 4-month review his visual acuity remained poor and progression of optic nerve atrophy was noted alongside the development of bilateral central scotomas. Further testing was congruent with a diagnosis of autoimmune optic retinopathy. We propose this to be secondary to his syphilitic infection. Syphilis is known as the "great mimicker," and despite being quite treatable, this case highlights ongoing complexity in the diagnosis and management of syphilis, unfortunately with a poor visual outcome.
Case Rep Ophthalmol 2019;10:81–88

https://ift.tt/2T0sVbz

Clonal analysis of early-stage bilateral papillary thyroid cancer identifies field cancerization

Abstract

Introduction

Bilaterality is a newly identified indicator for aggressive tumor behavior and poor outcome in papillary thyroid cancer. However, the clonal origin of these bilateral tumors remains unclear.

Methods

Here we analyzed 28 pairs of early-stage papillary thyroid cancers (stage I–II without extra-thyroidal extension, lymph node metastasis or distant metastasis) that underwent surgery at First Affiliated Hospital of Zhejiang University School of Medicine (Hangzhou, China). Genomic DNA was extracted from paraffin-embedded tissues after microdissection and analyzed for BRAF mutation and X-chromosome inactivation.

Results

A total of 16 patients (16/28, 57.1%) harbored different BRAF status in bilateral tumors. Fourteen patients were available for X-chromosome inactivation assay and 10 of them achieved informative results. Bilateral tumors from four cases had distinct patterns of X-chromosome inactivation. Combining the results of X-chromosome inactivation and BRAF analysis, we demonstrated that at least 64.3% (18/28) cases harbored discordant X-chromosome inactivation or BRAF status, indicating their independent clonal origin in bilateral tumors.

Conclusions

The present study confirms "field cancerization" in early-stage bilateral thyroid cancers, suggesting that these subtype papillary thyroid cancers should be treated as independent and localized tumors.

https://ift.tt/2GM6lge

Photodynamic enhancement of the activity of antibiotics used in urinary tract infections

Abstract

Photodynamic therapy (PDT) has been proven to kill different microbial cells. However, to our knowledge, none of the available reports describes the modulatory effect of this therapy on the antibacterial activity of antibiotics against Escherichia coli rods being the main causative agent of urinary tract infections (UTIs). Therefore, the aim of our study was to verify if the PDT can enhance the antibacterial activity of antibiotics recommended in the treatment of UTIs. An attempt to determine the optimal conditions of PDT to enhance the bactericidal activity of ciprofloxacin, amikacin, and colistin has been made. In order to find the optimal antimicrobial conditions, the efficacy of four protocols associated with the use of different energy doses (70 and 120 J/cm²) and chlorin e6 (Ce6) concentrations (50 and 100 μg/mL) has been verified. The antibacterial effect of combined PDT and antibiotics was assessed by the time-kill assay. The best results were achieved for Ce6 at a concentration of 100 μg/mL and the energy dose 120 J/cm² for bacterial suspensions treated with ciprofloxacin. Taken together, our results showed that PDT using Ce6 improves the antibacterial activity of antibiotics effectively inhibiting bacterial growth and being promising in the elimination of bacterial UTIs in humans.

https://ift.tt/2ICrtaD

HIV-Related Skin Disease in the Era of Antiretroviral Therapy: Recognition and Management

Abstract

Antiretroviral therapy (ART) has revolutionized the treatment and prognosis of people living with HIV (PLHIV). With increased survival and improved overall health, PLHIV are experiencing dermatologic issues both specific to HIV and common to the general population. In this new era of ART, it is crucial for dermatologists to have a strong understanding of the broad range of cutaneous disease and treatment options in this unique population. In this review, we outline the most common skin diseases in PLHIV, including HIV-associated malignancies, inflammatory conditions, and infections, and focus on the role of ART in altering epidemiology, clinical features, diagnosis, and treatment of cutaneous conditions.

https://ift.tt/2TiZoJs

Analysis of vegetation dynamics, drought in relation with climate over South Asia from 1990 to 2011

Abstract

Drought is the most complex climate-related disaster issue in South Asia, because of the various land-cover changes, vegetation dynamics, and climates. The aims of the current research work were to analyze the performance of AVHRR Normalized Difference Vegetation Index (NDVI) and spatiotemporal differences in vegetation dynamics on a seasonal basis by correlating the results with NASA's MERRA precipitation and air temperature for monitoring vegetation dynamics and drought over South Asia. Our approach is based on the use of AVHRR NDVI data and NASA's MERRA rainfall and air temperature data (1990–2011). Due to the low vegetation and dryness, the NDVI is more helpful in describing the drought condition in South Asia. There were rapid increases in NDVI, VHI, and VCI from April to October. Monthly NDVI, VHI, and VCI stabilize in September and improved once more in October and then show a declining trend in December. The monthly PCI, TCI, VHI, and VCI values showed that the South Asia goes through an extreme drought in 2000, which continues up to 2002, which lead the highest water stress. Spatial correlation maps among NDVI, precipitation, air temperature, VHI, and VCI on a seasonal basis. The correlation between NDVI and precipitation showed a significantly higher correlation value in JJA and SON seasons; the spatial correlation between NDVI and air temperature showed significant high values in DJF, JJA, and SON periods, while the correlation between VHI and TCI showed a significantly higher values in MAM and SON seasons, which indicated a good sign for dryness monitoring, mainly for farming regions during these seasons in South Asia. It was confirmed that these indexes are a comprehensive drought monitoring indicator and a step to monitoring the climate change in South Asia, which will play a relevant role ongoing studies on vegetation types, monitoring climate change, and drought over South Asia.

https://ift.tt/2Exwj4Y

Transcriptome analysis of Oryza sativa in responses to different concentrations of thiocyanate

Abstract

Effective concentrations of potassium thiocyanate (KSCN) to rice seedlings were experimentally determined using relative growth rate as a sensitive endpoint. Agilent 44-K rice microarray was used to profile the molecular responses of rice seedlings exposed to thiocyanate ion (SCN⁻) at three different effective concentrations (EC₁₀, EC₂₀, and EC₅₀). A total of 18,498 known genes were collected from SCN-treated rice microarray analysis. Out of all, 1603, 1882, and 5085 differentially expressed genes (DEGs) were observed at EC₁₀, EC₂₀, and EC₅₀ concentrations, respectively. More upregulated/downregulated DEGs were detected in shoots than in roots after SCN⁻ exposure. Gene functions and pathway enrichment analysis of DEGs indicated that different effective concentrations of SCN⁻ resulted in multiple enriched GO categories and KEGG pathways and outcomes were quite tissue-specific. Different regulations and adaptations of gene expression in molecular function (MF), biological process (BP), and cellular components (CC) were observed in rice tissues at different effective concentrations of SCN⁻, suggesting their different responsive and adaptive strategies. Information collected here presents a detailed description of SCN-induced alternations of gene expression in rice seedlings and provide valuable information for further searching specific genes participating in transportation, phytotoxic responses, and detoxification of SCN⁻ in rice seedlings.

https://ift.tt/2Vj5U09

Effects of individual ozone exposure on lung function in the elderly: a cross-sectional study in China

Abstract

The aim of this study was to assess the acute health effects of individual ozone (O₃) exposure on the respiratory system in the elderly. A total of 40 non-smoking elderly volunteers completed personal 24 h of measurement for O₃ and fine particulate matter (PM_2.5). To assess health effects, we measured the pulmonary function and five inflammatory biomarkers in exhaled breath condensate (EBC), including interleukin-2 (IL-2), interferon-γ (IFN-γ), prostaglandin E₂ (PGE₂), and tumor necrosis factor α/β (TNFα/β). We used the generalized additive model to analyze the association between O₃ and these health effects, after adjusting PM_2.5, BMI, and sex as confounders. As a result, we found a negative correlation between O₃ and forced vital capacity (FVC) or forced expiratory volume-one second (FEV1). With the increasing of O₃ by 10 μg/m³, FVC and FEV1 decreased by 0.13 L (95% CI 0.01, 0.26) and 0.11 L (95% CI 0.02, 0.20), respectively. We found no statistical significance between O₃ and biomarkers in EBC. The results suggested that individual 24-h O₃ exposure was associated with decreased pulmonary function in the elderly.

https://ift.tt/2ExucOq

Euphorbia leaf extract-assisted sustainable synthesis of Au NPs supported on exfoliated GO for superior activity on water purification: reduction of 4-NP and MB

Abstract

In the present work, the effect of graphene oxide (GO) architecture and synthesis of gold nanoparticles (Au_NPs) on the surface of GO by using Euphorbia leaf extract was investigated. The as-synthesized catalyst was utilized for reduction of 4-nitrophenol (4-NP) and methylene-blue (MB). The ethanol/water extract of the leaves of Euphorbia was found as a non-toxic, suitable, eco-friendly natural reducing agent in one-step generation of Au nanoparticles onto the GO. The catalyst was characterized by different analysis such as atomic force microscopy, powder X-ray diffraction, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, SEM-mapping, transmission electron microscopy, and atomic absorption spectrometry. The high catalytic performance of the surfactant exfoliated gold-GO (SE-Au_NPs/GO) towards the reduction of 4-NP to 4-aminophenol (4-AP) and reduction of MB to leucomethylene blue (LMB) under mild conditions, in water and at room temperature, was exhibited.

Graphical abstract

https://ift.tt/2Vj5Opj

The ubiquitin-like modifier FAT10 is required for normal IFN-γ production by activated CD8+ T cells

Publication date: April 2019

Source: Molecular Immunology, Volume 108

Author(s): Mei Min Mah, Michael Basler, Marcus Groettrup

Abstract

FAT10 is the only ubiquitin-like modifier which directly targets its substrate proteins for rapid degradation by the proteasome. While the conjugation and proteasomal targeting of FAT10 are fairly well understood, the biological functions of FAT10 have remained largely elusive. Here we have investigated the role of FAT10 in cytokine responses in mice upon viral infection. We used lymphocytic choriomeningitis virus (LCMV) infection of mice to induce the IFN-γ and TNF-α-dependent expression of FAT10. We found that TCR-stimulated splenocytes derived from LCMV-infected FAT10^−/− mice secreted less IFN-γ and expressed less mRNA for IL-12 p40 but secreted more IFN-α and IFN-β compared to FAT10^+/− mice. The reduction in IFN-γ secretion could be assigned to CD8⁺ T cells. Nevertheless, LCMV viral clearance was similar in FAT10^−/− as compared to FAT10^+/− mice. Since FAT10 has previously been reported to promote influenza A virus (IAV) replication in vitro we have studied the effect of FAT10 deficiency during IAV infection in mice. Unexpectedly, IAV titers and disease symptoms were not changed in FAT10^−/− mice even though the Fat10 mRNA was rapidly induced in the lung upon IAV infection. In conclusion, we find that FAT10 fine-tunes the balance of interferons during viral infection by lowering the production of type I and enhancing type II interferons.

https://ift.tt/2ICkaQf

Otorhinolaryngological manifestations and delayed diagnosis in Kawasaki Disease

Publication date: Available online 26 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): M. Rouault, A. Coudert, R. Hermann, Y. Gillet, E. Truy, S. Ayari-Khalfallah

Abstract

Objectives

Kawasaki disease (KD) is a febrile multisystemic vasculitis of unknown etiology whose coronary prognosis is improved by early diagnosis and management. The objective of this study was to describe ENT manifestations encountered and to look for a delayed diagnosis associated with these manifestations.

Methods

A retrospective descriptive single-center study was conducted in Lyon between January 2009 and December 2017. All children treated for Kawasaki disease were included in the study. Clinical, biological and cardiac ultrasound data were collected. According to the diagnosis made at the first medical visit, children were classified into two groups: diagnosis of ENT spectrum or non-ENT diagnosis. The diagnostic times were compared by a Student test.

Results

142 patients were included: 64 in the ENT diagnostic group, 78 in the non-ENT diagnostic group. When the initial diagnosis was of ENT spectrum, the diagnostic time of KD was significantly longer: 8.51 days vs 5.77 days - (p <0.01). The total duration of fever was also longer - 10.92 vs 8.32 days – (p = 0.013) - and the frequency of antibiotics intake more important - 92.2% vs 46.2% - (p <0.01). Four children underwent surgery in the ENT diagnostic group: two retro-pharyngeal abscesses, one paracentesis and one cervicectomy.

Conclusions

ENT manifestations are frequently at the forefront of KD and constitute a misleading clinical picture responsible for delayed diagnosis and potentially inappropriate medico-surgical management. It is necessary to provide more education to practitioners for earlier recognition of Kawasaki disease.

https://ift.tt/2To2wEd

Radiation Exposure during Videofluoroscopic Swallowing Studies in Young Children

Publication date: Available online 25 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Eun Jae Ko, In Young Sung, Kyoung Hyo Choi, Yong Gyu Kwon, Jisun Yoon, Taehoon Kim

Abstract

Objectives

Swallowing difficulties are best assessed by videofluoroscopic swallowing studies (VFSS). However, limiting radiation exposure is important, especially in young children. The purpose was to evaluate radiation dose in young children during VFSS, and to investigate factors associated with it.

Methods

Children with swallowing difficulty who underwent VFSS from February 2012 to July 2014 were recruited. Dose area product (DAP) and screening time were offered by the fluoroscopy machine, and effective dose was calculated from the DAP using a conversion coefficient published by the National Radiological Protection Board (NRPB-R262). The age, gender, height, weight, body mass index (BMI), body surface area (BSA), underlying disease of the subject children, and results of VFSS were investigated.

Results

In 89 children (mean age 1.57±2.17, 55 boys and 34 girls), mean effective dose was 0.29±0.20 mSv, mean DAP was 2.41±1.65 Gy cm², and mean screening time was 2.24±0.99 minutes. The effective dose correlated with the screening time (r=0.598, p<0.001), age (r=0.210, p=0.049), height (r=0.521, p<0.001), weight (r=0.461, p<0.001), and BSA (r=0.493, p<0.001). There was no such correlation with gender, BMI, underlying disease, or the results of VFSS.

Conclusion

s: The effective dose during VFSS (0.29 mSv) in young children, which is affected by screening time, age, and body size, is considerably lower than the pediatric radiation exposure limit of 1mSv per year. However more than 4 VFSS annually would exceed this limit. Our findings will help physicians to reduce the radiation exposure and provide a useful references for future pediatric VFSS guidelines.

https://ift.tt/2IDPLBb

F-BAR domain only protein 1 (FCHO1) deficiency is a novel cause of combined immune deficiency in humans

Publication date: Available online 26 February 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Enrica Calzoni, Craig D. Platt, Sevgi Keles, Hye Sun Kuehn, Sarah Beaussant-Cohen, Yu Zhang, Julia Pazmandi, Gaetana Lanzi, Francesca Pala, Azzeddine Tahiat, Hasibe Artac, Raul Jimenez Heredia, Jasmin Dmytrus, Ismail Reisli, Vedat Uygun, Dilara Uygun, Aysen Bingol, Erdem Basaran, Kamel Djenouhat, Nafissa Benhalla

https://ift.tt/2EvPLik

Traffic noise exposure of high-rise residential buildings in urban area

Abstract

Noise pollution is a major factor of environmental complaints in many cities, which has significant impacts on human health. As a dominating source of environmental noise, the impact of road traffic noise is increasing. Residents living in high-rise buildings along the main road are severely affected by traffic noise. In order to assess the noise level of urban area along the main road in Guangzhou, three buildings were selected to conduct traffic noise measurements, and the questionnaire about traffic noise impact on human being was completed. Through the questionnaire, around 70% of participants consider the traffic noise has negative effect, and about 60% of participants consider the noise has moderate or much higher impact on physical comfort. Around 65% of participants consider the noise had moderately or much higher impact on their psychological comfort. By analyzing the measured data, all of the measured noise levels in three buildings exceed the recommended limit of 55 dB (A) in the daytime and 45 dB (A) in the night for residence, and the exceeded value can be up to 16 dB (A). By comparing the fitting curve of noise level transfer function on each floor relative to the reference floor, the quadratic polynomial was selected to plot the transfer function rather than cubic polynomial.

https://ift.tt/2VoZJb9